This invention relates to amide and alkyl ester derivatives of pyrimido[4,5-b]quinolin-4(3H)-one-2-carboxylic acids and salts thereof as agents for the control of peptic ulcers in animals, including man.
A number of pyrimido[4,5-b]quinolines (1,3-diazo-acridines) are described in the art [J. Chem. Soc., 727 (1927); J. Hetero. Chem., 7, 99 (1970); J. Am. Chem. Soc., 78, 5108 (1956); and J. Chem. Soc., 552 (1948)]. However, none of them contain a carboxy group or functional derivative thereof, i.e., an ester, amide, acid chloride, with the exception of 2,4-dihydroxy-pyrimido[4,5-b]quinoline-5-carboxylic acid, its methyl ester, amide and acid chloride; 1,3-dimethyl-1,2,3,4-tetrahydro-pyrimido[4,5-b]quinolin-2,4-dione-5-carbox ylic acid methyl ester; and 10-methyl-2,3,4,10-tetrahydro-pyrimido-[4,5-b]quinolin-2,4-dione-5-carboxy lic acid and its methyl ester. The products were investigated as potential riboflavin antagonists. Taylor et al., J. Am. Chem. Soc., 78, 5108 (1956) describe 2-methylpyrimido[4,5-b]-quinolin-4(3H)-one. No 2-carboxy substituted derivatives are described in the literature.
Belgian Patent No. 813,571, granted Oct. 11, 1974, describes pyrimido-[4,5-b]quinolin-4(3H)-one-2-carboxylic acids, esters and simple amides (--CONH.sub.2) thereof, and corresponding 2-hydroxamic acids as antiallergy agents.
The compounds described herein are effective antiulcer agents via the intraperitoneal route of administration. Many of them are also active via the oral route of administration. These products not only accelerate healing of such ulcers but also prevent formation of ulcers and some decrease gastric acid output in animals, including humans. They can, therefore, be said to be useful for the control of gastric ulcers.